Guignard taught in Columbia City Schools for four years before moving to Philadelphia to attend medical college. She was an intern at the Women's Hospital for one year before returning to Columbia. specializing on obstetrics and pediatrics. She was also an attending physician on staff at the College for Women and
Columbia College from 1905 to 1908. Delivering babies at home exposed her to the health risks faced by the city's poorer residents, and she opened a small
maternity home in the 1920s. She served as the second assistant to the chief surgeon at Columbia Hospital and worked to improve services for women and children. She also created a training program for black midwives. She practiced medicine for over 55 years delivering over 1,000 babies throughout her career. Guignard was president of the Columbia Equal Suffrage League. After suffrage was won, she was co-founder of the Columbia
League of Women Voters, and state chair of the Social Hygiene Department of the South Carolina League of Women Voters. She was active in
Altrusa, and was honored by the local chapter in 1959, for her many years of service to the community. She was also honored in 1954 at her 50th anniversary ceremony of graduating from the Woman's Medical College of Pennsylvania.
Matilda Evans, a Black woman physician in Columbia, admired Guignard as a colleague, saying Guignard was one "whose soul is in the work of caring for and helping suffering humanity." Guignard and her sister Caroline funded a lecture series at the
University of South Carolina as a memorial to their brother, Gabriel Alexander Guignard, who died in 1926. Late in life, she donated the Guignard family property called
Still Hopes to the local Episcopal diocese to use as a retirement home. She attended the ground-breaking for Trinity Home, as the project was named, in 1960. ==Personal life ==